Improved knowledge about the particular brain regions that degenerate in frontotemporal lobar degeneration (FTLD) has led to specific predictions about what kinds of cognitive and emotional tasks would be most sensitive for detecting and following changes in function resulting from this disease. Experimental studies in animals and healthy human participants have led to the development of tasks tapping cognitive and emotional functions in the frontal and temporal lobes, but the value of these paradigms for tracking function in specific brain regions in neurodegenerative disease is unknown. The overarching goal of this project is to link performance on specific cognitive and behavioral tasks to regional pathology in FTLD measured with magnetic resonance imaging (MRI). Neuroimaging will be performed at high field-strength (4 Tesla) and will include perfusion and diffusion tensor imaging, analyzed using hand-traced regions of interest. Performance on these novel tasks will be correlatedwith regional cortical volumes, regional perfusion values and fractional anisotropy (FA) in specific white matter tracts. Correlations between these measures and real world performance, as rated by informants, will also be examined. The project will address three specific aims: 1) To define the relationship between changes in the dorsal frontal regions and specific aspects of cognitive control and regulation of emotion, 2) To define the relationship between changes in the ventral and medial prefrontal regions and activation of the emotional systems for monitoring of behavior, and 3) To define the relationship between changes in the anterior temporal lobe and comprehension of verbal and non-verbal stimuli. Linkage of these functions to specific regions in the brain could lead to their use in clinical diagnosis, monitoring the course of disease progression, and evaluating the effectiveness of present and future treatments. Furthermore, these studies will facilitate a better understanding of brain-behavior relationships in regions with still poorly understood functions.